INHIBITION OF RNA AND DNA-SYNTHESIS IN UV-IRRADIATED NORMAL HUMAN FIBROBLASTS IS CORRELATED WITH PYRIMIDINE(6-4)PYRIMIDONE PHOTOPRODUCT FORMATION

UV-irradiation of living cells results in an inhibition of RNA and DNA synthesis. The purpose of this study was to determine whether specifi c photoproducts or the total combined yield of lesions were responsibl e for these effects. Asynchronously dividing human fibroblasts from no rmal donors were irradiated with UVC (254 nm), broad spectrum UVB (290 -320 + nm, Westinghouse FS20 lamp) or narrow spectrum UVB (310-315 nm, Philips TL01 lamp) at fluences which induce known yields of cyclobuta ne pyrimidine dimers, pyrimidine (6-4) pyrimidone photoproducts or Dew ar isomers. DNA synthesis was approximately 3-4 times more sensitive t o both UVC and UVB irradiation than RNA synthesis. The immediate inhib ition of RNA and DNA synthesis was correlated with (6-4) rather than o verall photoproduct formation suggesting that the (6-4) photoproduct i s the mediator of these inhibitory effects. In support of this suggest ion we found that photoreactivation of cells cultured from the marsupi al, mouse Sminthopsis crassicaudata, resulted in removal of 70% of pyr imidine dimers from the overall genome, but had only a slight effect o n the recovery of RNA synthesis.